Development of a new delivery system consisting in "drug - in cyclodextrin - in nanostructured lipid carriers" for ketoprofen topical delivery
Development of a new delivery system consisting in "drug - in cyclodextrin - in nanostructured lipid carriers" for ketoprofen topical delivery
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DOI：
10.1016/j.ejpb.2011.07.015
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发表时间：
2012-01-01
影响因子：
4.9
通讯作者：
Mura, P.
中科院分区：
文献类型：
--
作者：
Cirri, M.;Bragagni, M.;Mura, P.
为了提高酮洛芬的治疗效果，开发了一种新的基于药物环糊精（Cd）络合和负载到纳米结构脂质载体（NLC）中的给药系统。所提出的策略利用了Cds的增溶和稳定特性以及NLC的延长释放、高耐受性和经皮吸收增强剂特性。测试了两种不同的聚合物Cd，即β-Cd-环氧氯丙烷聚合物（EPI-beta Cd）和羧甲基化-β-Cd-环氧氯丙烷聚合物（EPI-CM beta Cd），并比较了两种不同的获得固体酮洛芬-聚合物Cd络合物的技术（即共研磨和共冻干），以研究制备方法对最终产物的物理化学性质的影响。EPI-beta Cd比EPI-CM beta Cd更有效地提高酮洛芬的溶解度和溶出特性。在干燥条件下的共研磨是最好的制备技术的固体药物-镉系统，允许获得均匀的纳米范围内的无定形颗粒。通过超声处理获得由Compritol（R）888 ATO（甘油基山嵛酸酯）和Labrafac Lipophile的混合物组成的NLC。空的和加载的NLC都适当地表征了粒径、pH、包封率和药物释放行为。最好的（药物-镉）-加载NLC系统，配制成黄原胶水凝胶，表现出药物渗透性能明显优于那些平原药物悬浮液或平原载药NLC，凭借同时利用环糊精的增溶作用和渗透增强剂性能的NLC。(C)2011 Elsevier B. V.保留所有权利。
A new delivery system based on drug cyclodextrin (Cd) complexation and loading into nanostructured lipid carriers (NLC) has been developed to improve ketoprofen therapeutic efficacy. The proposed strategy exploits both the solubilizing and stabilizing properties of Cds and the prolonged release, high tolerability and percutaneous absorption enhancer properties of NLC. Two different polymeric Cds, i.e. beta-Cd-epichlorohydrin polymer (EPI-beta Cd) and carboxymethylathed-beta-Cd-epichlorohydrin polymer (EPI-CM beta Cd) were tested and two different techniques to obtain solid ketoprofen-polymeric Cd complexes (i.e. co-grinding and co-lyophilization) were compared, to investigate the influence of the preparation method on the physicochemical properties of the end product. EPI-beta Cd was more effective than EPI-CM beta Cd in enhancing the solubility and dissolution properties of ketoprofen. Co-grinding in dry conditions was the best preparation technique of solid drug-Cd systems, allowing obtainment of homogeneous amorphous particles of nanometric range. NLC consisting in a mixture of Compritol (R) 888 ATO (glyceryl behenate) and Labrafac Lipophile were obtained by ultrasonication. Both empty and loaded NLC were suitably characterized for particle size, pH, entrapment efficiency and drug release behavior. The best (drug-Cd)-loaded NLC system, formulated into a xanthan hydrogel, exhibited drug permeation properties clearly better than those of the plain drug suspension or the plain drug-loaded NLC, in virtue of the simultaneous exploitation of the solubilizing effect of cyclodextrin and the penetration enhancer properties of NLC. (C) 2011 Elsevier B.V. All rights reserved.